Genetska variabilnost serotoninske poti v povezavi z občutenjem pooperativne bolečine

Kanalec, Eva (author), Dolžan, Vita (mentor)

Serotonin v telesu hkrati opravlja vlogo živčnega prenašalca in hormona. Kot živčni prenašalec znotraj centralnega živčnega sistema vpliva na različne vedenjske funkcije, med katere sodijo razpoloženje, spomin, odziv na stres in občutenje bolečine. V poti biosinteze, razgradnje in delovanja serotonina (serotoninska pot) med drugimi sodelujejo tudi encimi sinteze serotonina, med njimi je najpomembnejši triptofan hidroksilaza (TPH2), serotoninski receptorji (HTR) in serotoninski transporter (SERT). Pri operaciji raka dojke je pri več kot 50 % bolnic prisotna akutna pooperativna bolečina, ki pa se v nekaterih primerih nadaljuje tudi po zaključenem okrevanju, takrat govorimo o kronični pooperativni bolečini. Po prestani operaciji se bolnice pogosto soočajo tudi z nevropatsko bolečino. Namen magistrskega dela je bil preveriti, ali je genetska variabilnost v serotoninski poti povezana z občutenjem bolečine, odgovorom na protibolečinsko zdravljenje in počutjem bolnic po operaciji raka dojke, ki je vključevala odstranitev pazdušnih bezgavk. V raziskavo smo vključili 113 bolnic po operaciji raka dojke, ki je vključevala odstranitev pazdušnih bezgavk, in so po operaciji kot protibolečinsko zdravljenje prejemale tramadol s paracetamolom. Z molekularnogenetskimi metodami smo izvedli genotipizacijo polimorfizmov HTR1A rs6295, HTR1B rs1321204, TPH2 rs1843809, TPH2 rs7305115, TPH2 rs4290270 in TPH2 rs4570625, SLC6A4 5-HTTLPR in SLC6A4 rs25531. S statistično analizo smo preverili povezanost preiskovanih genetskih polimorfizmov z občutenjem bolečine v prvem mesecu po operaciji, prisotnostjo kronične in nevropatske bolečine, izraženostjo simptomov anksioznosti in depresije ter kvaliteto življenja en mesec ter eno leto po operaciji. Rezultati naše raziskave kažejo na povezanost polimorfizmov TPH2 rs4570625, SLC6A4 5-HTTLPR in SLC6A4 rs25531 z občutenjem bolečine v prvem mesecu po operaciji. HTR1A rs6295 je bil povezan z izraženostjo simptomov anksioznosti, HTR1A rs6295 in TPH2 rs4570625 pa z izraženostjo simptomov depresije štiri tedne in eno leto po operaciji. Polimorfizmi HTR1A rs6295, TPH2 rs4570625 in SLC6A4 5-HTTLPR so bili povezani tudi z nekaterimi kazalci kvalitete življenja štiri tedne in eno leto po operaciji. Ni pa nam uspelo potrditi povezave med polimorfizmi serotoninske poti in prisotnostjo kronične in nevropatske bolečine eno leto po operaciji. Ugotovitve naše in podobnih raziskav s področja farmakogenetike so pomembne za razumevanje povezanosti genetskih dejavnikov z občutenjem bolečine. To bi v prihodnje omogočilo učinkovitejše zdravljenje pooperativne bolečine in boljšo kvaliteto življenja.

• Language: Slovenian
• Keywords: serotonin, polimorfizem, bolečina, rak dojke, tramadol
• Work type: Master's thesis/paper
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2024
• PID: 20.500.12556/RUL-164692
• Publication date in RUL: 07.11.2024

Secondary language

• Language: English
• Title: Genetic variability in serotonin metabolism and pathways in relation to postoperative pain sensation

Abstract

Serotonin has an important role as a neurotransmitter as well as a hormone. Mood, memory, stress response, and pain perception are all affected by this neurotransmitter within the central nervous system. The biosynthesis, degradation, and function of serotonin (serotonin pathway) involves several enzymes, including tryptophan hydroxylase (TPH2), serotonin receptors (HTR), and the serotonin transporter (SERT). More than 50 % of patients who undergo breast cancer surgery experience acute postoperative pain. However, some patients continue to experience pain after complete recovery, at which point it can be considered chronic postoperative pain. It is also common for patients to experience neuropathic pain following surgery. The aim of this master's thesis was to evaluate the association of genetic variability in the serotonin pathway with pain sensation, pain medication response, and well-being among patients after breast cancer surgery, which also involved axillary lymphadenectomy. We enrolled 113 patients following breast cancer surgery with axillary lymphadenectomy treated with tramadol and paracetamol for pain relief. Using molecular genetic methods, we performed genotyping of HTR1A rs6295, HTR1B rs1321204, TPH2 rs1843809, TPH2 rs7305115, TPH2 rs4290270 and TPH2 rs4570625, SLC6A4 5-HTTLPR and SLC6A4 rs25531. Based on a statistical analysis we determined the association between genetic polymorphisms and pain sensation in the first month following surgery, chronic and neuropathic pain, anxiety and depression symptoms, and the impact on the quality of life four weeks and one year following surgery. In our study, we demonstrated that the TPH2 rs4570625, SLC6A4 5-HTTLPR, and SLC6A4 rs25531 polymorphisms were associated with pain sensation within the first month following surgery. The HTR1A rs6295 polymorphism was associated with anxiety symptoms and the TPH2 rs4570625 polymorphism with depression symptoms four weeks and one year after surgery. In addition, HTR1A rs6295, TPH2 rs4570625 and SLC6A4 5-HTTLPR polymorphisms were partially associated with the quality of life four weeks and one year after surgery. In our study, polymorphisms of the serotonin pathway were not associated with chronic and neuropathic pain one year after surgery. Our findings, together with similar studies in the field of pharmacogenetics, provide valuable insights into the influence of genetic factors on pain sensation. In the future this would allow for more effective postoperative pain treatment and better quality of life.

• Keywords: serotonin, polymorphism, pain, breast cancer, tramadol